At-home wireless monitoring of acute hemodynamic disturbances to detect sleep apnea and sleep stages via a soft sternal patch.

Obstructive sleep apnea (OSA) affects more than 900 million adults globally and can create serious health complications when untreated; however, 80% of cases remain undiagnosed. Critically, current diagnostic techniques are fundamentally limited by low throughputs and high failure rates. Here, we report a wireless, fully integrated, soft patch with skin-like mechanics optimized through analytical and computational studies to capture seismocardiograms, electrocardiograms, and photoplethysmograms from the sternum, allowing clinicians to investigate the cardiovascular response to OSA during home sleep tests. In preliminary trials with symptomatic and control subjects, the soft device demonstrated excellent ability to detect blood-oxygen saturation, respiratory effort, respiration rate, heart rate, cardiac pre-ejection period and ejection timing, aortic opening mechanics, heart rate variability, and sleep staging. Last, machine learning is used to autodetect apneas and hypopneas with 100% sensitivity and 95% precision in preliminary at-home trials with symptomatic patients, compared to data scored by professionally certified sleep clinicians.

Effects of Surface Topography and Chemistry on Polyether-Ether-Ketone (PEEK) and Titanium Osseointegration.

STUDY DESIGN: An in vivo study examining the functional osseointegration of smooth, rough, and porous surface topographies presenting polyether-ether-ketone (PEEK) or titanium surface chemistry. OBJECTIVE: To investigate the effects of surface topography and surface chemistry on implant osseointegration. SUMMARY OF BACKGROUND DATA: Interbody fusion devices have been used for decades to facilitate fusion across the disc space, yet debate continues over their optimal surface topography and chemistry. Though both factors influence osseointegration, the relative effects of each are not fully understood. METHODS: Smooth, rough, and porous implants presenting either a PEEK or titanium surface chemistry were implanted into the proximal tibial metaphyses of 36 skeletally mature male Sprague Dawley rats. At 8 weeks, animals were euthanized and bone-implant interfaces were subjected to micro-computed tomography analysis (n = 12), histology (n = 4), and biomechanical pullout testing (n = 8) to assess functional osseointegration and implant fixation. RESULTS: Micro-computed tomography analysis demonstrated that bone ingrowth was 38.9 ±â€Š2.8% for porous PEEK and 30.7 ±â€Š3.3% for porous titanium (P = 0.07). No differences in fixation strength were detected between porous PEEK and porous titanium despite titanium surfaces exhibiting an overall increase in bone-implant contact compared with PEEK (P < 0.01). Porous surfaces exhibited increased fixation strength compared with smooth and rough surfaces regardless of surface chemistry (P < 0.05). Across all groups both surface topography and chemistry had a significant overall effect on fixation strength (P < 0.05), but topography accounted for 65.3% of the total variance (ω = 0.65), whereas surface chemistry accounted for 5.9% (ω = 0.06). CONCLUSIONS: The effect of surface topography (specifically porosity) dominated the effect of surface chemistry in this study and could lead to further improvements in orthopedic device design. The poor osseointegration of existing smooth PEEK implants may be linked more to their smooth surface topography rather than their material composition. LEVEL OF EVIDENCE: N/A.

Porous PEEK improves the bone-implant interface compared to plasma-sprayed titanium coating on PEEK.

Polyether-ether-ketone (PEEK) is one of the most common materials used for load-bearing orthopaedic devices due to its radiolucency and favorable mechanical properties. However, current smooth-surfaced PEEK implants can lead to fibrous encapsulation and poor osseointegration. This study compared the in vitro and in vivo bone response to two smooth PEEK alternatives: porous PEEK and plasma-sprayed titanium coatings on PEEK. MC3T3 cells were grown on smooth PEEK, porous PEEK, and Ti-coated PEEK for 14 days and assayed for calcium content, osteocalcin, VEGF and ALP activity. Osseointegration was investigated by implanting cylindrical implants into the proximal tibiae of male Sprague Dawley rats for 8 weeks. Bone-implant interfaces were evaluated using µCT, histology and pullout testing. Cells on porous PEEK surfaces produced more calcium, osteocalcin, and VEGF than smooth PEEK and Ti-coated PEEK groups. Bone ingrowth into porous PEEK surfaces was comparable to previously reported porous materials and correlated well between µCT and histology analysis. Porous PEEK implants exhibited greater pullout force, stiffness and energy-to-failure compared to smooth PEEK and Ti-coated PEEK, despite Ti-coated PEEK exhibiting a high degree of bone-implant contact. These results are attributed to increased mechanical interlocking of bone with the porous PEEK implant surface. Overall, porous PEEK was associated with improved osteogenic differentiation in vitro and greater implant fixation in vivo compared to smooth PEEK and Ti-coated PEEK. These results suggest that not all PEEK implants inherently generate a fibrous response and that topography has a central role in determining implant osseointegration.

Biological evaluation and finite-element modeling of porous poly(para-phenylene) for orthopaedic implants.

Poly(para-phenylene) (PPP) is a novel aromatic polymer with higher strength and stiffness than polyetheretherketone (PEEK), the gold standard material for polymeric load-bearing orthopaedic implants. The amorphous structure of PPP makes it relatively straightforward to manufacture different architectures, while maintaining mechanical properties. PPP is promising as a potential orthopaedic material; however, the biocompatibility and osseointegration have not been well investigated. The objective of this study was to evaluate biological and mechanical behavior of PPP, with or without porosity, in comparison to PEEK. We examined four specific constructs: 1) solid PPP, 2) solid PEEK, 3) porous PPP and 4) porous PEEK. Pre-osteoblasts (MC3T3) exhibited similar cell proliferation among the materials. Osteogenic potential was significantly increased in the porous PPP scaffold as assessed by ALP activity and calcium mineralization. In vivo osseointegration was assessed by implanting the cylindrical materials into a defect in the metaphysis region of rat tibiae. Significantly more mineral ingrowth was observed in both porous scaffolds compared to the solid scaffolds, and porous PPP had a further increase compared to porous PEEK. Additionally, porous PPP implants showed bone formation throughout the porous structure when observed via histology. A computational simulation of mechanical push-out strength showed approximately 50% higher interfacial strength in the porous PPP implants compared to the porous PEEK implants and similar stress dissipation. These data demonstrate the potential utility of PPP for orthopaedic applications and show improved osseointegration when compared to the currently available polymeric material. STATEMENT OF SIGNIFICANCE: PEEK has been widely used in orthopaedic surgery; however, the ability to utilize PEEK for advanced fabrication methods, such as 3D printing and tailored porosity, remain challenging. We present a promising new orthopaedic biomaterial, Poly(para-phenylene) (PPP), which is a novel class of aromatic polymers with higher strength and stiffness than polyetheretherketone (PEEK). PPP has exceptional mechanical strength and stiffness due to its repeating aromatic rings that provide strong anti-rotational biaryl bonds. Furthermore, PPP has an amorphous structure making it relatively easier to manufacture (via molding or solvent-casting techniques) into different geometries with and without porosity. This ability to manufacture different architectures and use different processes while maintaining mechanical properties makes PPP a very promising potential orthopaedic biomaterial which may allow for closer matching of mechanical properties between the host bone tissue while also allowing for enhanced osseointegration. In this manuscript, we look at the potential of porous and solid PPP in comparison to PEEK. We measured the mechanical properties of PPP and PEEK scaffolds, tested these scaffolds in vitro for osteocompatibility with MC3T3 cells, and then tested the osseointegration and subsequent functional integration in vivo in a metaphyseal drill hole model in rat tibia. We found that PPP permits cell adhesion, growth, and mineralization in vitro. In vivo it was found that porous PPP significantly enhanced mineralization into the construct and increased the mechanical strength required to push out the scaffold in comparison to PEEK. This is the first study to investigate the performance of PPP as an orthopaedic biomaterial in vivo. PPP is an attractive material for orthopaedic implants due to the ease of manufacturing and superior mechanical strength.

Effect of porous orthopaedic implant material and structure on load sharing with simulated bone ingrowth: A finite element analysis comparing titanium and PEEK.

Osseointegration of load-bearing orthopaedic implants, including interbody fusion devices, is critical to long-term biomechanical functionality. Mechanical loads are a key regulator of bone tissue remodeling and maintenance, and stress-shielding due to metal orthopaedic implants being much stiffer than bone has been implicated in clinical observations of long-term bone loss in tissue adjacent to implants. Porous features that accommodate bone ingrowth have improved implant fixation in the short term, but long-term retrieval studies have sometimes demonstrated limited, superficial ingrowth into the pore layer of metal implants and aseptic loosening remains a problem for a subset of patients. Polyether-ether-ketone (PEEK) is a widely used orthopaedic material with an elastic modulus more similar to bone than metals, and a manufacturing process to form porous PEEK was recently developed to allow bone ingrowth while preserving strength for load-bearing applications. To investigate the biomechanical implications of porous PEEK compared to porous metals, we analyzed finite element (FE) models of the pore structure-bone interface using two clinically available implants with high (> 60%) porosity, one being constructed from PEEK and the other from electron beam 3D-printed titanium (Ti). The objective of this study was to investigate how porous PEEK and porous Ti mechanical properties affect load sharing with bone within the porous architectures over time. Porous PEEK substantially increased the load share transferred to ingrown bone compared to porous Ti under compression (i.e. at 4 weeks: PEEK = 66%; Ti = 13%), tension (PEEK = 71%; Ti = 12%), and shear (PEEK = 68%; Ti = 9%) at all time points of simulated bone ingrowth. Applying PEEK mechanical properties to the Ti implant geometry and vice versa demonstrated that the observed increases in load sharing with PEEK were primarily due to differences in intrinsic elastic modulus and not pore architecture (i.e. 4 weeks, compression: PEEK material/Ti geometry = 53%; Ti material/PEEK geometry = 12%). Additionally, local tissue energy effective strains on bone tissue adjacent to the implant under spinal load magnitudes were over two-fold higher with porous PEEK than porous Ti (i.e. 4 weeks, compression: PEEK = 784 ± 351 microstrain; Ti = 180 ± 300 microstrain; and 12 weeks, compression: PEEK = 298 ± 88 microstrain; Ti = 121 ± 49 microstrain). The higher local strains on bone tissue in the PEEK pore structure were below previously established thresholds for bone damage but in the range necessary for physiological bone maintenance and adaptation. Placing these strain magnitudes in the context of literature on bone adaptation to mechanical loads, this study suggests that porous PEEK structures may provide a more favorable mechanical environment for bone formation and maintenance under spinal load magnitudes than currently available porous 3D-printed Ti, regardless of the level of bone ingrowth.

Impaction durability of porous polyether-ether-ketone (PEEK) and titanium-coated PEEK interbody fusion devices.

BACKGROUND CONTEXT: Various surface modifications, often incorporating roughened or porous surfaces, have recently been introduced to enhance osseointegration of interbody fusion devices. However, these topographical features can be vulnerable to damage during clinical impaction. Despite the potential negative impact of surface damage on clinical outcomes, current testing standards do not replicate clinically relevant impaction loading conditions. PURPOSE: The purpose of this study was to compare the impaction durability of conventional smooth polyether-ether-ketone (PEEK) cervical interbody fusion devices with two surface-modified PEEK devices that feature either a porous structure or plasma-sprayed titanium coating. STUDY DESIGN/SETTING: A recently developed biomechanical test method was adapted to simulate clinically relevant impaction loading conditions during cervical interbody fusion procedures. METHODS: Three cervical interbody fusion devices were used in this study: smooth PEEK, plasma-sprayed titanium-coated PEEK, and porous PEEK (n=6). Following Kienle et al., devices were impacted between two polyurethane blocks mimicking vertebral bodies under a constant 200 N preload. The posterior tip of the device was placed at the entrance between the polyurethane blocks, and a guided 1-lb weight was impacted upon the anterior face with a maximum speed of 2.6 m/s to represent the strike force of a surgical mallet. Impacts were repeated until the device was fully impacted. Porous PEEK durability was assessed using micro-computed tomography (µCT) pre- and postimpaction. Titanium-coating coverage pre- and postimpaction was assessed using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy. Changes to the surface roughness of smooth and titanium-coated devices were also evaluated. RESULTS: Porous PEEK and smooth PEEK devices showed minimal macroscopic signs of surface damage, whereas the titanium-coated devices exhibited substantial visible coating loss. Quantification of the porous PEEK deformation demonstrated that the porous structure maintained a high porosity (>65%) following impaction that would be available for bone ingrowth, and exhibited minimal changes to pore size and depth. SEM and energy dispersive X-ray spectroscopy analysis of titanium-coated devices demonstrated substantial titanium coating loss after impaction that was corroborated with a decrease in surface roughness. Smooth PEEK showed minimal signs of damage using SEM, but demonstrated a decrease in surface roughness. CONCLUSION: Although recent surface modifications to interbody fusion devices are beneficial for osseointegration, they may be susceptible to damage and wear during impaction. The current study found porous PEEK devices to show minimal damage during simulated cervical impaction, whereas titanium-coated PEEK devices lost substantial titanium coverage.

Getting PEEK to Stick to Bone: The Development of Porous PEEK for Interbody Fusion Devices.

Interbody fusion cages are routinely implanted during spinal fusion procedures to facilitate arthrodesis of a degenerated or unstable vertebral segment. Current cages are most commonly made from polyether-ether-ketone (PEEK) due to its favorable mechanical properties and imaging characteristics. However, the smooth surface of current PEEK cages may limit implant osseointegration and may inhibit successful fusion. We present the development and clinical application of the first commercially available porous PEEK fusion cage (COHERE®, Vertera, Inc., Atlanta, GA) that aims to enhance PEEK osseointegration and spinal fusion outcomes. The porous PEEK structure is extruded directly from the underlying solid and mimics the structural and mechanical properties of trabecular bone to support bone ingrowth and implant fixation. Biomechanical testing of the COHERE® device has demonstrated greater expulsion resistance versus smooth PEEK cages with ridges and greater adhesion strength of porous PEEK versus plasma-sprayed titanium coated PEEK surfaces. In vitro experiments have shown favorable cell attachment to porous PEEK and greater proliferation and mineralization of cell cultures grown on porous PEEK versus smooth PEEK and smooth titanium surfaces, suggesting that the porous structure enhances bone formation at the cellular level. At the implant level, preclinical animal studies have found comparable bone ingrowth into porous PEEK as those previously reported for porous titanium, leading to twice the fixation strength of smooth PEEK implants. Finally, two clinical case studies are presented demonstrating the effectiveness of the COHERE® device in cervical spinal fusion.

Local deformation behavior of surface porous polyether-ether-ketone.

Surface porous polyether-ether-ketone has the ability to maintain the tensile monotonic and cyclic strength necessary for many load bearing orthopedic applications while providing a surface that facilitates bone ingrowth; however, the relevant deformation behavior of the pore architecture in response to various loading conditions is not yet fully characterized or understood. The focus of this study was to examine the compressive and wear behavior of the surface porous architecture using micro Computed Tomography (micro CT). Pore architectures of various depths (~0.5-2.5mm) and pore sizes (212-508µm) were manufactured using a melt extrusion and porogen leaching process. Compression testing revealed that the pore architecture deforms in the typical three staged linear elastic, plastic, and densification stages characteristic of porous materials. The experimental moduli and yield strengths decreased as the porosity increased but there was no difference in properties between pore sizes. The porous architecture maintained a high degree of porosity available for bone-ingrowth at all strains. Surface porous samples showed no increase in wear rate compared to injection molded samples, with slight pore densification accompanying wear.

Do Surface Porosity and Pore Size Influence Mechanical Properties and Cellular Response to PEEK?

BACKGROUND: Despite its widespread use in orthopaedic implants such as soft tissue fasteners and spinal intervertebral implants, polyetheretherketone (PEEK) often suffers from poor osseointegration. Introducing porosity can overcome this limitation by encouraging bone ingrowth; however, the corresponding decrease in implant strength can potentially reduce the implant's ability to bear physiologic loads. We have previously shown, using a single pore size, that limiting porosity to the surface of PEEK implants preserves strength while supporting in vivo osseointegration. However, additional work is needed to investigate the effect of pore size on both the mechanical properties and cellular response to PEEK. QUESTIONS/PURPOSES: (1) Can surface porous PEEK (PEEK-SP) microstructure be reliably controlled? (2) What is the effect of pore size on the mechanical properties of PEEK-SP? (3) Do surface porosity and pore size influence the cellular response to PEEK? METHODS: PEEK-SP was created by extruding PEEK through NaCl crystals of three controlled ranges: 200 to 312, 312 to 425, and 425 to 508 µm. Micro-CT was used to characterize the microstructure of PEEK-SP. Tensile, fatigue, and interfacial shear tests were performed to compare the mechanical properties of PEEK-SP with injection-molded PEEK (PEEK-IM). The cellular response to PEEK-SP, assessed by proliferation, alkaline phosphatase activity, vascular endothelial growth factor production, and calcium content of osteoblast, mesenchymal stem cell, and preosteoblast (MC3T3-E1) cultures, was compared with that of machined smooth PEEK and Ti6Al4V. RESULTS: Micro-CT analysis showed that PEEK-SP layers possessed pores that were 284 ± 35 µm, 341 ± 49 µm, and 416 ± 54 µm for each pore size group. Porosity and pore layer depth ranged from 61% to 69% and 303 to 391 µm, respectively. Mechanical testing revealed tensile strengths > 67 MPa and interfacial shear strengths > 20 MPa for all three pore size groups. All PEEK-SP groups exhibited > 50% decrease in ductility compared with PEEK-IM and demonstrated fatigue strength > 38 MPa at one million cycles. All PEEK-SP groups also supported greater proliferation and cell-mediated mineralization compared with smooth PEEK and Ti6Al4V. CONCLUSIONS: The PEEK-SP formulations evaluated in this study maintained favorable mechanical properties that merit further investigation into their use in load-bearing orthopaedic applications and supported greater in vitro osteogenic differentiation compared with smooth PEEK and Ti6Al4V. These results are independent of pore sizes ranging 200 µm to 508 µm. CLINICAL RELEVANCE: PEEK-SP may provide enhanced osseointegration compared with current implants while maintaining the structural integrity to be considered for several load-bearing orthopaedic applications such as spinal fusion or soft tissue repair.

High-strength, surface-porous polyether-ether-ketone for load-bearing orthopedic implants.

Despite its widespread clinical use in load-bearing orthopedic implants, polyether-ether-ketone (PEEK) is often associated with poor osseointegration. In this study, a surface-porous PEEK material (PEEK-SP) was created using a melt extrusion technique. The porous layer was 399.6±63.3 µm thick and possessed a mean pore size of 279.9±31.6 µm, strut spacing of 186.8±55.5 µm, porosity of 67.3±3.1% and interconnectivity of 99.9±0.1%. Monotonic tensile tests showed that PEEK-SP preserved 73.9% of the strength (71.06±2.17 MPa) and 73.4% of the elastic modulus (2.45±0.31 GPa) of as-received, injection-molded PEEK. PEEK-SP further demonstrated a fatigue strength of 60.0 MPa at one million cycles, preserving 73.4% of the fatigue resistance of injection-molded PEEK. Interfacial shear testing showed the pore layer shear strength to be 23.96±2.26 MPa. An osseointegration model in the rat revealed substantial bone formation within the pore layer at 6 and 12 weeks via microcomputed tomography and histological evaluation. Ingrown bone was more closely apposed to the pore wall and fibrous tissue growth was reduced in PEEK-SP when compared to non-porous PEEK controls. These results indicate that PEEK-SP could provide improved osseointegration while maintaining the structural integrity necessary for load-bearing orthopedic applications.

Local strategies to prevent and treat osteoporosis.

Despite advances in systemic osteoporosis therapeutic outcomes, management of fragility fractures and implant fixation in osteoporotic bone remain difficult clinical challenges. Low initial bone density and a prolonged healing response can lead to fracture nonunion and aseptic implant loosening. Local treatment strategies could be used to prevent fracture, accelerate healing, and increase implant fixation by locally stimulating anabolic pathways or inhibiting catabolic pathways. Local strategies under investigation include direct drug release from injectable materials or implant surface coatings. Common locally delivered drugs include bisphosphonates, parathyroid hormone, and bone morphogenetic proteins, yet additional compounds targeting novel pathways in bone biology are also being actively explored. Mechanical stimulation via low intensity pulsed ultrasound, alone or in combination with drug therapy, may also prove effective to promote local bone healing and implant fixation within osteoporotic bone.